The major aim of the proposed investigation is to assess tyrosinase activity and to resolve its isozymes in human melanomas and to characterize the presence of suspected endogenous inhibitors of the enzyme. The research will also include a study of the effects of a relatively wide spectrum of chemical agents which have shown inhibitory action on tyrosinase activity of vertebrates. The proposed research is expected to provide not only a better understanding of the human melanoma, specifically, and melanin pigmentation, in general, but also may be of use for future studies dealing with chemotherapy of the disease. A sensitive and specific C14-radiometric assay of tyrosinase and some promising biochemical approaches for the isolation and characterization of tyrosinase isozymes and endogenous inhibitor(s) are available. The tyrosinase activity of melanoma specimens in the presence of test drugs can be specifically determined by the radiometric assay, thus permitting an accurate measurement of the activation or inhibition of tyrosinase by drugs utilized.